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PL
Artykuł powstał na podstawie rozprawy doktorskiej pt.: 'Syntetyczne peptydy jako materiały do budowy czujników' nagrodzonej przez Komitet Chemii Analitycznej PAN w 2021 roku w konkursie na najlepsze prace doktorskie, nagroda ufundowana przez firmę LGC Standards.
EN
Proteins are synthesized only by living organisms. Today, we are able to receive them by recombinant protein expression in bacterial cells. This technique is very useful and gives satisfactory amount of desirable material but it precludes the possibility of introduction of some chemical modifications that are often obligatory. For this reason, chemical synthesis of longer peptide chains is still important and is the object of scientists attention. Over the last century, notion of peptide synthesis took a new meaning. Nowadays, we know a number of innovative methods and also automated devices which help us to make progress in this area. Nevertheless, the synthesis of longer, more complicated peptide chains and proteins still constitutes a problem. Native chemical ligation (NCL) has facilitated the synthesis of numerous complex peptide and protein targets. Expansion of ligation techniques has allowed the entry of peptides into the world of therapeutic drugs [1]. NCL reactions are carried out in aqueous solution and give good yields. Due to mild conditions, NCL overcomes racemic and solubility problems encountered in classical peptide synthesis using protected fragments. The challenge is to synthesize the C-terminal thioester-containing peptide necessary for the transesterification reaction, which is the first step of linking the peptide fragments [2]. In this review we discuss the evolution, advantages and potential applications of chemical ligation reactions. In the first part of this article we described the utility of native chemical ligation approach to non-cysteine containing peptides. This part details a number of important approaches to the synthesis of peptides bearing a C-terminal thioester. Contemporary applications of these techniques to the total chemical synthesis of proteins are also presented.
EN
Proteins are biological macromolecules affecting very important functions in the body. They are involved in many biochemical processes. They can perform catalytic functions acting as enzymes. They also participate in the transport of many small molecules and ions – for example one molecule of hemoglobin carries four molecules of oxygen. In addition, proteins serve as antibodies and are involved in transmission of nerve impulses as receptor proteins. Because peptides and proteins perform so important functions, to study them it is essential to obtain these compounds in the greatest possible amounts. The compounds can be obtained generally by three main methods: • by isolation of the native peptides and proteins • by expression in microorganisms • by chemical synthesis. Each of the above methods has its advantages and disadvantages, but only the chemical synthesis gives the possibility to introduce modifications to the structure of the resulting protein, such as the insertion of new functional groups, to give the product in the final form and with satisfactory yield. In this review we present the application of chemical ligation methods in the synthesis of peptides and proteins. We describe in details mechanism of native chemical ligation method and the conditions necessary to carry the reaction [1]. The synthesis of long polypeptide chains by kinetically controlled ligation (KCL) is also depicted [2]. This part of the paper also details a number of approaches to noncysteine containing peptides by chemical ligation methods.
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